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Database: UniProt
Entry: P39040
LinkDB: P39040
Original site: P39040 
ID   TYTR_CRIFA              Reviewed;         491 AA.
AC   P39040;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   11-DEC-2013, entry version 100.
DE   RecName: Full=Trypanothione reductase;
DE            Short=TR;
DE            EC=1.8.1.12;
DE   AltName: Full=N(1),N(8)-bis(glutathionyl)spermidine reductase;
GN   Name=TPR;
OS   Crithidia fasciculata.
OC   Eukaryota; Euglenozoa; Kinetoplastida; Trypanosomatidae;
OC   Leishmaniinae; Crithidia.
OX   NCBI_TaxID=5656;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1453951; DOI=10.1111/j.1365-2958.1992.tb01766.x;
RA   Aboagye-Kwarteng T., Smith K., Fairlamb A.H.;
RT   "Molecular characterization of the trypanothione reductase gene from
RT   Crithidia fasciculata and Trypanosoma brucei: comparison with other
RT   flavoprotein disulphide oxidoreductases with respect to substrate
RT   specificity and catalytic mechanism.";
RL   Mol. Microbiol. 6:3089-3099(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   PubMed=1542316; DOI=10.1016/0166-6851(92)90243-D;
RA   Field H., Cerami A., Henderson G.B.;
RT   "Cloning, sequencing, and demonstration of polymorphism in
RT   trypanothione reductase from Crithidia fasciculata.";
RL   Mol. Biochem. Parasitol. 50:47-56(1992).
RN   [3]
RP   PROTEIN SEQUENCE OF 39-62, AND CHARACTERIZATION.
RX   PubMed=3718941; DOI=10.1021/bi00360a007;
RA   Shames S.L., Fairlamb A.H., Cerami A., Walsh C.T.;
RT   "Purification and characterization of trypanothione reductase from
RT   Crithidia fasciculata, a newly discovered member of the family of
RT   disulfide-containing flavoprotein reductases.";
RL   Biochemistry 25:3519-3526(1986).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), AND DISULFIDE BOND.
RX   PubMed=8477734; DOI=10.1111/j.1432-1033.1993.tb17734.x;
RA   Bailey S., Smith K., Fairlamb A.H., Hunter W.N.;
RT   "Substrate interactions between trypanothione reductase and N1-
RT   glutathionylspermidine disulphide at 0.28-nm resolution.";
RL   Eur. J. Biochem. 213:67-75(1993).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX   PubMed=1522596; DOI=10.1016/0022-2836(92)90701-K;
RA   Hunter W.N., Bailey S., Habash J., Harrop S.J., Helliwell J.R.,
RA   Aboagye-Kwarteng T., Smith K., Fairlamb A.H.;
RT   "Active site of trypanothione reductase. A target for rational drug
RT   design.";
RL   J. Mol. Biol. 227:322-333(1992).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX   PubMed=15299452; DOI=10.1107/S0907444993011898;
RA   Bailey S., Fairlamb A.H., Hunter W.N.;
RT   "Structure of trypanothione reductase from Crithidia fasciculata at
RT   2.6-A resolution; enzyme-NADP interactions at 2.8-A resolution.";
RL   Acta Crystallogr. D 50:139-154(1994).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS).
RX   PubMed=15299300; DOI=10.1107/S0907444994010772;
RA   Strickland C.L., Puchalski R., Savvides S.N., Karplus P.A.;
RT   "Overexpression of Crithidia fasciculata trypanothione reductase and
RT   crystallization using a novel geometry.";
RL   Acta Crystallogr. D 51:337-341(1995).
CC   -!- FUNCTION: Trypanothione is the parasite analog of glutathione;
CC       this enzyme is the equivalent of glutathione reductase.
CC   -!- CATALYTIC ACTIVITY: Trypanothione + NADP(+) = trypanothione
CC       disulfide + NADPH.
CC   -!- COFACTOR: Binds 1 FAD per subunit.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 7.5-8.0;
CC   -!- SUBUNIT: Homodimer.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- PTM: The N-terminus is blocked.
CC   -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC   -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC       oxidoreductase family.
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DR   EMBL; Z12618; CAA78264.1; -; Genomic_DNA.
DR   EMBL; M73323; AAA30321.1; -; mRNA.
DR   EMBL; M73324; AAA30322.1; -; Genomic_DNA.
DR   EMBL; M73325; AAA30323.1; -; Genomic_DNA.
DR   PIR; S28002; S28002.
DR   PDB; 1FEA; X-ray; 2.20 A; A/B/C/D=2-491.
DR   PDB; 1FEB; X-ray; 2.00 A; A/B=2-491.
DR   PDB; 1FEC; X-ray; 1.70 A; A/B=2-491.
DR   PDB; 1TYP; X-ray; 2.80 A; A/B=1-487.
DR   PDB; 1TYT; X-ray; 2.60 A; A/B=1-487.
DR   PDB; 2TPR; X-ray; 2.40 A; A/B=2-491.
DR   PDBsum; 1FEA; -.
DR   PDBsum; 1FEB; -.
DR   PDBsum; 1FEC; -.
DR   PDBsum; 1TYP; -.
DR   PDBsum; 1TYT; -.
DR   PDBsum; 2TPR; -.
DR   ProteinModelPortal; P39040; -.
DR   SMR; P39040; 1-487.
DR   BindingDB; P39040; -.
DR   ChEMBL; CHEMBL5394; -.
DR   BioCyc; MetaCyc:MONOMER-13293; -.
DR   EvolutionaryTrace; P39040; -.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0015036; F:disulfide oxidoreductase activity; IEA:InterPro.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR   GO; GO:0015042; F:trypanothione-disulfide reductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR   Gene3D; 3.30.390.30; -; 1.
DR   InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer.
DR   InterPro; IPR013027; FAD_pyr_nucl-diS_OxRdtase.
DR   InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR   InterPro; IPR023753; Pyr_nucl-diS_OxRdtase_FAD/NAD.
DR   InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR   InterPro; IPR001327; Pyr_OxRdtase_NAD-bd_dom.
DR   InterPro; IPR001864; Trypnth_redctse.
DR   Pfam; PF00070; Pyr_redox; 1.
DR   Pfam; PF07992; Pyr_redox_2; 1.
DR   Pfam; PF02852; Pyr_redox_dim; 1.
DR   PRINTS; PR00368; FADPNR.
DR   PRINTS; PR00470; TRYPANRDTASE.
DR   SUPFAM; SSF55424; SSF55424; 1.
DR   TIGRFAMs; TIGR01423; trypano_reduc; 1.
DR   PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Direct protein sequencing; Disulfide bond;
KW   FAD; Flavoprotein; NADP; Oxidoreductase; Redox-active center.
FT   CHAIN         1    491       Trypanothione reductase.
FT                                /FTId=PRO_0000067988.
FT   NP_BIND      35     51       FAD.
FT   ACT_SITE    461    461       Proton acceptor.
FT   DISULFID     52     57       Redox-active.
FT   VARIANT     479    479       Q -> E.
FT   CONFLICT     16     16       G -> R (in Ref. 2; AAA30322/AAA30323).
FT   CONFLICT     62     62       L -> Y (in Ref. 3; AA sequence).
FT   CONFLICT    297    297       D -> E (in Ref. 2; AAA30321/AAA30322/
FT                                AAA30323).
FT   CONFLICT    454    454       F -> V (in Ref. 2; AAA30322/AAA30323).
FT   STRAND        4     10
FT   HELIX        14     27
FT   STRAND       31     36
FT   STRAND       38     41
FT   TURN         42     44
FT   HELIX        51     55
FT   HELIX        57     75
FT   HELIX        76     79
FT   HELIX        85     87
FT   HELIX        92    115
FT   STRAND      120    131
FT   STRAND      134    142
FT   STRAND      147    158
FT   STRAND      162    164
FT   HELIX       172    174
FT   HELIX       178    181
FT   STRAND      189    194
FT   HELIX       198    210
FT   STRAND      216    227
FT   HELIX       232    244
FT   STRAND      247    251
FT   STRAND      255    260
FT   STRAND      266    270
FT   STRAND      275    283
FT   STRAND      287    290
FT   HELIX       292    294
FT   HELIX       296    299
FT   STRAND      322    324
FT   HELIX       326    329
FT   HELIX       335    350
FT   STRAND      364    366
FT   STRAND      368    370
FT   STRAND      372    376
FT   HELIX       379    385
FT   STRAND      387    396
FT   HELIX       399    404
FT   STRAND      411    418
FT   TURN        419    421
FT   STRAND      423    431
FT   HELIX       434    446
FT   HELIX       451    455
FT   HELIX       465    469
FT   STRAND      475    479
FT   STRAND      482    484
SQ   SEQUENCE   491 AA;  53229 MW;  EF749215A16F9187 CRC64;
     MSRAYDLVVI GAGSGGLEAG WNAASLHKKR VAVIDLQKHH GPPHYAALGG TCVNVGCVPK
     KLMVTGANYM DTIRESAGFG WELDRESVRP NWKALIAAKN KAVSGINDSY EGMFADTEGL
     TFHQGFGALQ DNHTVLVRES ADPNSAVLET LDTEYILLAT GSWPQHLGIE GDDLCITSNE
     AFYLDEAPKR ALCVGGGYIS IEFAGIFNAY KARGGQVDLA YRGDMILRGF DSELRKQLTE
     QLRANGINVR THENPAKVTK NADGTRHVVF ESGAEADYDV VMLAIGRVPR SQTLQLDKAG
     VEVAKNGAIK VDAYSKTNVD NIYAIGDVTD RVMLTPVAIN EGAAFVDTVF ANKPRATDHT
     KVACAVFSIP PMGVCGYVEE DAAKKYDQVA VYESSFTPLM HNISGSTYKK FMVRIVTNHA
     DGEVLGVHML GDSSPEIIQS VAICLKMGAK ISDFYNTIGV HPTSAEELCS MRTPAYFYQK
     GKRVEKIDSN L
//
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